Small rodents with long lifespans — such as the squirrel, chipmunk and muskrat — have evolved a previously undiscovered anti-cancer mechanism that seems to be different from any found in humans or other large mammals, according to a new study in the journal Aging Cell.
Biologists at the University of Rochester who led the study are hopeful that further investigation of the mechanism will help prevent cancer in humans, once the role of stem cells in the process is fully understood.
"We haven't come across this anticancer mechanism before because it doesn't exist in the two species most often used for cancer research: mice and humans," says Vera Gorbunova, assistant professor of biology at the University of Rochester, and a principal investigator of the study. "Mice are short-lived and humans are large-bodied. But this mechanism appears to exist only in small, long-lived animals."
Cells of these rodents could be hypersensitive to cues from the surrounding tissue, Gorbunova said. If the cells sense that conditions aren't favorable for growth, they restrict cell division, which would inhibit tumor growth and prevent metastases.
Rodents, as regular readers of this blog know, range in size from tiny mice to the human-sized capybara found in Brazil. By comparing the sizes and lifespans of several different-sized but related animals, Gorbunova discovered that telomerase - an enzyme that can increase the lifetime of cells, but can also boost the rate of cancer - is highly active in small rodents, but not in large ones.
Until this finding, biologists thought that a long-lived animal needed to suppress telomerase activity to guard against cancer, because telomerase helps cells reproduce, and cancer is essentially runaway cellular reproduction. It would stand to reason that an animal living for 70-plus years would have many chances for its cells to reproduce and mutate into cancer.
But Gorbunova and colleagues showed that body mass, not life expectancy, regulated the expression of telomerase. A higher number of cells in the body increases the likelihood that one of the cells will become cancerous. Humans, as large animals, would likely develop cancer much more frequently and much earlier if we didn't suppress our telomerase.
But why isn't cancer more prevalent in small animals like the common grey squirrel, which lives for 24 years or more?
Gorbunova found that the squirrel, naked mole-rat, chipmunk, muskrat, and chinchilla express high levels of telomerase, which would be expected to increase their cancer risk over their long lifetimes. But these species have developed a mechanism to counteract the high telomerase activity and remain cancer free for the duration of their lives.
"Squirrels know a cure for cancer," says Gorbunova. "Short-lived small species display continuous rapid proliferation of their cells, but these long-lived rodents have somehow found a way to slow down that proliferation when they need to."
Gorbunova thinks that squirrels and similar rodents have evolved a monitoring function inside their cells that can differentiate between healthy reproduction and runaway cancerous reproduction; they can then slow or inhibit the division if needed.
Gorbunova is now trying to isolate this mechanism and determine whether it can help human cells thwart the onset of tumor growth.